Biomedical Engineering Reference
In-Depth Information
Such an approach has been reported to be useful in the development of probes for
cell tracking by surface enhanced raman scattering. Gold nanoparticles were sur-
face functionalized with the SV40 NLS, which led to accumulation of the nanopar-
ticles in the nucleus of HeLa cells (Xie et al.
2009
). Quantum dots conjugated to
the amino group of the mitochondrial targeting sequence, Mito-8 were reported to
be colocalized in the mitochondria (Hoshino et al.
2004
). Chlorotoxin conjugated
iron oxide nanoparticles coated with a copolymer of chitosan-PEG-PEI were found
to specifically translocate to the nucleus of cancer cells permitting a dual targeting
approach to a specific cell type and an organelle within the cell type; this approach
was successful
in vivo
, both for imaging and therapeutic purposes Kievit (
2010
).
Modification with a leader sequence peptide has also been applied to creating
delivery systems for mitochondria. A mitochondrial leader peptide (MLP), derived
from the nucleo-cytosol expressed but mitochondria localized ornithine transcar-
bamylase was recently used to render polyethylenimine (PEI) mitochondriotropic
(Lee et al.
2007
). PEI had been developed in the mid 1990s as a versatile vector for
gene and oligonucleotide transfer into cells in culture and
in vivo
(Boussif et al.
1995
; Demeneix and Behr
2005
). Lee et al. (
2007
) conjugated the mitochondrial
leader peptide to PEI via a disulfide bond and confirmed the complex formation of
PEI-MLP with DNA by a gel retardation assay. In vitro delivery tests of rhodamine-
labeled DNA into living cells demonstrated that PEI-MLP/DNA complexes were
localized at mitochondrial sites in contrast to controls carried out with PEI-DNA
complexes lacking MLP. The author's data suggest that PEI-MLP can deliver DNA
to the mitochondrial sites and may be useful for the development of direct mito-
chondrial gene therapy, a strategy for the cure of mitochondrial DNA diseases
proposed earlier (Seibel et al.
1995
; Weissig and Torchilin
2000, 2001a, b
) as an
alternative to allotropic expression (Ellouze et al.
2008
; Oca-Cossio et al.
2003
;
Zullo
2001
; Gray et al.
1996
).
3.2
Nanocarriers Prepared from Self-assembling Molecules
with Known Sub-cellular Accumulation
All the examples discussed in the previous section share a common assumption that
unless a targeting ligand is incorporated into the design, the nanocarriers would
remain in the endolysosomal compartment. However it is interesting to also con-
sider the disposition of a nanocarrier made exclusively of a molecule with a predis-
position for a sub-cellular compartment. A good example of a molecule that has a
strong affinity for a sub-cellular compartment and that is also capable of self assem-
bling to form a potential carrier system is the mitochondriotropic amphiphile
dequalinium chloride. Vesicles prepared exclusively from dequalinium chloride
(called DQAsomes) have been explored for the delivery of several bioactive mol-
ecules to mitochondria (D'Souza et al.
2003, 2005, 2008
; Weissig et al.
2000,
2001
). Most recently, the antitumor efficiency of DQAsomal encapsulated pacli-
taxel was enhanced by modifying the DQAsomal surface with folic acid (FA)
(Vaidya et al.
2009
). However, DQAsomes currently serve as a preliminary proof
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